Phospholipase Cγ1 controls surface expression of TRPC3 through an intermolecular PH domain
Phospholipase Cγ1 controls surface expression of TRPC3 through an intermolecular PH domain
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DOI：
10.1038/nature03340
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发表时间：
2005-03-03
期刊：
影响因子：
64.8
通讯作者：
Snyder, SH
中科院分区：
文献类型：
--
作者：
van Rossum, DB;Patterson, RL;Snyder, SH
许多离子通道受脂类(1-3)调节，但在大多数离子通道中还没有发现显著的脂结合基序。最近，我们报道了磷脂酶CGamma1(PLC-Gamma1)结合并调节TRPC3通道(4)，这是激动剂诱导细胞内钙内流的组成部分。这种相互作用需要PLC-Gamma1中的一个结构域，该结构域包括部分Pleckstrin同源(PH)结构域-一个共识的脂结合和蛋白质结合序列(5，6)。我们已经开发了一种完形算法来检测到到目前为止不可见的PH和PH样结构域，现在报道PLC-Gamma1的部分PH结构域与TRPC3中互补的部分PH样结构域相互作用，诱导TRPC3的脂结合和细胞表面表达。我们的发现意味着PH结构域的丰度比以前认识的要多得多，并表明分子间PH样结构域代表着一种广泛的信号模式。
Many ion channels are regulated by lipids(1-3), but prominent motifs for lipid binding have not been identified in most ion channels. Recently, we reported that phospholipase Cgamma1 (PLC-gamma1) binds to and regulates TRPC3 channels(4), components of agonist-induced Ca2+ entry into cells. This interaction requires a domain in PLC-gamma1 that includes a partial pleckstrin homology (PH)domain - a consensus lipid-binding and protein-binding sequence(5,6). We have developed a gestalt algorithm to detect hitherto 'invisible' PH and PH-like domains, and now report that the partial PH domain of PLC-gamma1 interacts with a complementary partial PH-like domain in TRPC3 to elicit lipid binding and cell-surface expression of TRPC3. Our findings imply a far greater abundance of PH domains than previously appreciated, and suggest that intermolecular PH-like domains represent a widespread signalling mode.